Adequate consumption of polyunsaturated fatty acids (PUFA) is vital for neurodevelopment and neuroprotection. Previously, we established a TBI model using controlled cortical impact (CCI) to produce severe traumatic brain injury (TBI) and tested the effect of severe DHA depletion in the brain on the outcome of TBI in C57BL/6 mice. Using this model, we demonstrated an important influence of the brain DHA status on TBI outcome. We subsequently examined the DHA effect in a moderately DHA-depleted model which is more realistic in humans. In a mouse model with the brain DHA reduced by 35% which is comparable to the DHA status in modern human brains, we demonstrated that increasing the brain DHA level even from a moderately DHA-depleted state can reduce neuroinflammation and improve functional recovery after TBI. As modern diets have low omega-3 fatty acids and can lead to moderate DHA deficiency in humans, results from this study may present strong possibility of using nutritional remediation as a tool to enhance recovery from brain injury. Although our findings suggested possible improvement of recovery outcome by increasing dietary omega-3 PUFA in humans after TBI, the CCI model we used is not a realistic model for human TBI. Repeated mild traumatic brain injury (rmTBI) has been identified as a high-risk factor for dementia at a later stage in humans, however, animal models to replicate complex features of human rmTBI and/or to evaluate long-term effects on brain function were not established. During this review period, we established an rmTBI model using recently developed Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) which was shown to be a reliable rodent model to mimic many of the functional and pathological characteristics of TBI in humans. Adult C57BL/6 male mice were subjected to CHIMERA for three consecutive days 24 h apart, and behavioral outcomes and neuropathology were assessed. Repeated CHIMERA (rCHIMERA) resulted in motor deficits at 3 days and learning and memory impairments which were sustained up to 6-months post injury. GFAP and TNF- gene expression was increased within a day while astrogliosis and microgliosis were induced starting from day 1 up to 6.5 months after rCHIMERA with upregulated GFAP and Iba-1 protein levels. rCHIMERA also induced APP protein deposition from day 1 to day 7, but diminished by 1 month. In conclusion, we established a mouse model of TBI using rCHIMERA that produces long-lasting cognitive impairments with astrogliosis and microgliosis, which will allow us to test the effects of synaptamide and its analogues as well as diets for long-term consequences relevant to human rmTBI.